Author/Editor		Grujić, Mirjana
Title		Pomen intracelularnih interakcij bestatina in aktinonina pri njunem antiproliferativnem delovanju na celični liniji U937 in K562
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		2002
Volume		str. 81
Language		slo
Abstract		Actinonin and bestatin are aminopeptidase (AP) inhibitors of microbial origin, which compromise proliferation of various tumour cells. In our previous study of the mechanisms of antiproliferative activity of AP inhibitors on leukaemia cells (U937 and K562) we focused our attention on cell surface AP. We discovered that actinonin and bestatin do not compromise proliferation of leukaemia cells through the inhibition of any AP tested; the IC50 values for inhibition of cell proliferation are much higher than ICSo values for inhibition of cell surface AP activities (Grujic, 2000). In this study we showed that chemical instability of inhibitors in cell culture is not the cause for these differences in ICSO values of inhibitors; the inhibitory activity of the medium of cells did not change over a five day long experiment. We also detected bestatin in the medium of cells using HPLC. Further we measured activities of soluble AP in cell culture and observed that activities of soluble AP constitute only 10-13% of total extracellular AP activity (activity of soluble AP and activity of cell surface AP). Thus even soluble AP, that actinonin and bestatin bind to, are not the cause for the much higher ICso values of inhibitors that inhibit cell proliferation than ICso values of those that inhibit cell surface AP activity. In the next study we examined the influence of the inhibition of xenobiotic transport on antiproliferative activity of actinonin and bestatin on leukaemia cells. We used buthionine sulfoximine (BSO), which is an indirect inhibitor of the transporter multidrug resistanceassociated protein (MRP), MK-571, a specific inhibitor of MRP, and verapamil, a competitive inhibitor of transporter P-glycoprotein (P-gp). (Abstract truncated at 2000 characters).
Descriptors		TUMOR CELLS, CULTURED STREPTOMYCES AMINOPEPTIDASES CELL DIVISION DRUG INTERACTIONS XENOBIOTICS BUTHIONINE SULFOXIMINE VERAPAMIL P-GLYCOPROTEIN CYTOSOL SPECTRUM ANALYSIS, MASS